No question about it, all around the world, raves are the hottest thing since disco. Might even be hotter, but one has to be way under 30 to know for sure.

Raves mean, first of all, music and dancing. Raves are characterized by music of the techno persuasion. Most parents have sampled this music while waiting at a stoplight next to a car full of young people - unless they have teenagers in the house, in which case there's probably no way to escape it. Because, like its progenitor, rock, techno music is LOUD.

Not surprisingly, since they cater to a mostly college crowd, raves are characterized by some rebellion against the adult world. First, they delight in really bad spelling (we think it's deliberate). Next, they go from 9-6. That's 9PM to 6AM, and that's how they separate out the rest of us.

The reigning attitude at a rave is expressed in the acronym PLUR, which stands for Peace, Love, Unity and Respect. But that's not all that permeates the rave ambience.

The dark side

PLUR notwithstanding, there is a darker side to raves, and it goes by the seductive name of Ecstasy. Ecstasy (or MDMA, 3, 4-methylenedioxymethylamphetamine) is a derivative of amphetamine, more familiarly known as speed. Amphetamines and other related derivatives are powerful stimulants of the central nervous system. Unfortunately there seems to be a lot of it circulating at raves these days.

The immediate effects of Ecstasy ingestion include increased heart and breathing rate as well as reduced appetite. Large doses may result in fever and sweating, headache, dizziness or even collapse. What's worse, since Ecstasy is manufactured underground, it's ingredients are never certain.

"Sometimes the tablets contain only caffeine," says Professor Jean-Luc Veuthey, of the Department of Analytical Pharmaceutical Chemistry, University of Geneva. "Then it's not very dangerous, just expensive - at least for caffeine. The problem is in certain cases the tablets contain atropine, which is a poison, or cocaine or even heroin." Death due to fatal overdosing or through allergic reactions has also been reported.

Prof. Veuthey has been working on new methods to detect the presence of Ecstasy in biological fluids. One method using Capillary Electrophoresis (CE) with UV detection has been established earlier [1]. Currently his group is evaluating the power of CE coupled to Electrospray Ionization Mass Spectrometry (ESI-MS), on instruments his institution purchased from Hewlett-Packard [2].

Figure 1: Analysis of tablets containing amphetamines by CE with UV detection

Exciting technique

Prof. Veuthey's team examined approximately 50 tablets from drug seizures by CE with UV detection. Ecstasy-like derivatives were detected in more than 50% of them. Often, though, they were just mixtures of caffeine, aspirin and lactose.

"The method is able to resolve all amphetamines of interest in less than 8 minutes," says Prof. Veuthey. "Furthermore, we can note that this method presents the advantage of separating the amphetamines and the interfering substances in two different clusters". (Fig. 1).

The Department of Analytical Pharmaceutical Chemistry is cooperating with the Forensic Institutes. The CE-method has been successfully validated and is now used in this lab, as well as in the laboratory of the Scientific Police in Lausanne, to check tablets from seizures of suspected drugs for Ecstasy and others constituents. These labs find this technique more than adequate for their purposes. "The CE/UV method is easy, inexpensive, and can be handled in any laboratory," Prof. Veuthey says.

More structural information

CE with UV detection is appropriate for the quantitation of analytes yielding chromophores, as shown for the analysis of tablets containing amphetamines.

Going one step further, the analysis of drugs in body fluids, e.g. urine, remains a challenge. Here more precise information about the analytes as well as impurities or UV "ghost peaks" is needed.

In addition, the analysis of natural non-UV absorbing products might be mandatory without prior modification which would enable UV-detection. "Derivatization of non-UV absorbing species is not desired", Prof. Veuthey says, "we need to analyze original products".

Accordingly, Prof. Veuthey's group explored the capabilities of CE coupled to ESI-MS. Chemometric tools were used to optimize the parameters of a CE-ESI-MS method for the analysis of illicit drugs in body fluids [2]. Figure 2 shows the Total Ion Electropherogram (a) and the Extracted Ion Electropherogram (b) of the analysis of a urine sample (after liquid-liquid-extraction) spiked with amphetamines. Structural information about the constituents, including Ecstasy (MDMA), can be achieved within a couple of minutes.

Figure 2: Analysis of urine spiked with amphetamines by CE-ESI-MS(plus insert = mass spectrum of MDMA)

"Ecstasy affects the central nervous system and with regular consumption it can induce irreversible damage", says Prof. Veuthey. Chronic abuse of amphetamines often leads to hallucinations and psychosis. Depression and deep sleep have been experienced upon withdrawal. Even worse, the rave culture, where a lot of Ecstasy is consumed, has not yet reached a decade's age. Long-term effects may not yet be fully understood.

References:

1. "Analysis of Amphetamines by Capillary Electrophoresis and Liquid Chromatography - Applications to Drug Seizures and Cross-Validation", F. Sadeghipour, E. Varesio, C.Giroud, L. Rivier, and J.-L. Veuthey, Forensic Science International, 86, 1997, 1-13

2. "Optimization of CE-ESI-MS Parameters for the Analysis of Ecstasy and Derivatives in Urine", E. Varesio, S. Cherkaoui, and J.-L. Veuthey, J. High Resol. Chromatogr., 21, 1998, 653-657